When should beta (beta blockers) blockers be started in patients with esophageal varices?

When to Start Beta Blockers in Esophageal Varices

Nonselective beta-blockers should be started immediately upon detection of medium or large esophageal varices (>5mm) that have not bled, as they reduce first bleeding risk from 30% to 14% and improve mortality. 1

Primary Prophylaxis Based on Varix Size

Medium/Large Varices (>5mm)

• Start nonselective beta-blockers (NSBBs) immediately upon endoscopic diagnosis in all patients with medium or large varices who have not bled 1, 2
• This represents the strongest indication, with meta-analysis showing one bleeding episode prevented for every 10 patients treated 1
• Alternative option is endoscopic variceal ligation (EVL), with choice based on local expertise, patient preference, and presence of high-risk stigmata 1, 3
• EVL is preferred over NSBBs when high-risk bleeding stigmata are present (cherry red spots, red wale marks) 1

Small Varices (≤5mm) with High-Risk Features

• Start NSBBs if Child-Pugh class B or C cirrhosis is present 1, 2
• Start NSBBs if red wale marks are visible on varices 1, 2
• These high-risk patients benefit from early initiation despite smaller varix size 1

Small Varices (≤5mm) without High-Risk Features

• NSBBs can be used to slow progression from small to large varices (37% progression with placebo vs 11% with nadolol at 3 years), but long-term benefit is not well established 1, 2
• If NSBBs are not started, perform surveillance EGD every 2 years (or annually if decompensation occurs) 1
• The 2007 AASLD guidelines note higher adverse event withdrawal rates (11% vs 1% placebo) must be weighed against uncertain benefit in this population 1

No Varices

• Do not start NSBBs, as they do not prevent varix development 1
• Repeat screening EGD in 2-3 years for compensated cirrhosis 1

Dosing and Titration

• Propranolol: Start 40 mg once daily, titrate to maximal tolerated dose (not to heart rate target) 2, 4
• Nadolol: Start 40 mg once daily, titrate to maximal tolerated dose 1
• Long-acting propranolol 80-160 mg daily can improve compliance, but maximum dose should be reduced to 160 mg daily in patients with ascites 2
• Continue indefinitely once started, as discontinuation increases bleeding risk 1, 2

Secondary Prophylaxis (After Variceal Bleeding)

• Start NSBBs plus EVL combination therapy - this is superior to either modality alone for preventing rebleeding 2
• NSBBs can be initiated as early as 12-18 hours after endoscopic band ligation, rather than waiting the traditional 6 days 5
• Continue combination therapy indefinitely 2

Special Populations

Pregnancy

• Start NSBBs (propranolol preferred) for medium/large varices identified on screening EGD performed in second trimester 1
• NSBBs may be considered even for small varices in pregnancy due to hemodynamic changes that increase bleeding risk, though evidence is lacking 1
• EVL is preferred if high-risk stigmata present 1

Post-HCV Cure

• Discontinue NSBBs if post-SVR liver stiffness <12 kPa and platelets >150 G/L, as this rules out clinically significant portal hypertension 1
• Continue NSBBs if liver stiffness >25 kPa (rules in clinically significant portal hypertension) 1
• Perform EGD if liver stiffness 20-25 kPa and start NSBBs if varices present 1

Mechanism and Monitoring

• NSBBs reduce portal pressure through β1-mediated decreased cardiac output and β2-mediated splanchnic vasoconstriction 1, 2
• Selective beta-blockers (atenolol, metoprolol) are suboptimal and should not be used 1, 2
• Monitor heart rate, blood pressure, and renal function regularly, especially in advanced liver disease 2, 4

Key Contraindications

• Asthma, severe COPD, heart block, significant bradycardia, hypotension, decompensated heart failure 2
• In acute variceal bleeding, temporarily suspend beta-blockers until hemodynamic stability achieved 1

Common Pitfalls

• Do not use nitrates alone for primary prophylaxis - associated with increased mortality, especially in patients >50 years 4
• Do not use shunt therapy or sclerotherapy for primary prophylaxis - higher mortality and encephalopathy risk 4
• Do not delay NSBB initiation in medium/large varices waiting for "optimal timing" - start immediately upon diagnosis 1
• Do not target heart rate reduction of 25% from baseline as the primary endpoint - titrate to maximal tolerated dose instead 2